Immunogens comprising capsular saccharide antigens conjugated to carrier proteins are well known in the art. Conjugation converts T-independent antigens into T-dependent antigens, thereby enhancing memory responses and allowing protective immunity to develop, and the prototype conjugate vaccine was for Haemophilus influenzae type b (Hib) [e.g. see chapter 14 of ref. 1]. Since the Hib vaccine, conjugated saccharide vaccines for protecting against Neisseria meningitidis (meningococcus) and against Streptococcus pneumoniae (pneumococcus) have been developed. Other organisms where conjugate vaccines are of interest are Streptococcus agalactiae (group B streptococcus) [2], Pseudomonas aeruginosa [3] and Staphylococcus aureus [4].
Conjugate vaccines for N. meningitidis serogroup C have been approved for human use, and include Menjugate™ [5], Meningitec™ and NeisVac-C™. Mixtures of conjugates from each of serogroups A, C, W135 and Y have been reported [e.g. refs. 6-9], including the Menactra™ product. Other mixtures of conjugated antigens include: (i) meningococcal A/C mixtures [10, 11]; (ii) the PrevNar™ product [12] containing seven pneumococcal conjugates; (iii) mixed meningococcal and Hib conjugates [13, 14]; and (iv) combined meningococcal, pneumococcal and Hib conjugates [15].
Problems when dealing with conjugate vaccines include stability, batch-to-batch consistency and contamination. In Hib vaccines, for instance, catalytic depolymerisation of the saccharide has been reported [16], and conjugates of the serogroup A meningococcus capsule are readily hydrolyzed [17]. Instability of conjugates undesirably leads to a reduction in effective dose of immunogenic conjugate over time, variation between batches, and increased levels of uncharacterized breakdown products. References 18 & 19 discuss issues concerning stability testing of Hib conjugate vaccines.
Furthermore, quality control of glycoconjugate vaccines typically requires monitoring of impurities in the vaccine and monitoring of the protein integrity (i.e. denaturation).
In addition to glycoconjugate vaccines, other protein antigen-containing vaccines are also known, e.g. serogroup meningococcus B, hepatitis B virus, diphtheria, tetanus, and acellular pertussis vaccines.
Consequently, vaccines are frequently monitored after manufacture, during storage, and/or prior to administration to ensure their suitability for administration to a patient.
It is an object of the invention to provide modifications and improvements in the quality control of vaccines for assessing their stability, integrity and/or contamination.